Abstract

Follicular dendritic cells (FDCs) are found in all secondary lymphoid tissues, where they function as a repository of antigens
to maintain long‐term IgG and IgE responses. Antigens are trapped and retained on FDCs in the form of immune complexes; and
while most immune complexes require large quantities to induce an immune response, FDC‐trapped antigens are remarkably immunogenic
and only a few picogram can induce microgram concentrations of a specific antibody. In addition to providing antigens, FDCs
provide a number of additional signals (e.g. BAFF, IL‐6) that further contribute to antibody production. In addition to their
contributions to immunity in health, FDCs are involved in some pathological situations including HIV/AIDS (human immunodeficiency
virus/acquired immune deficiency syndrome), sarcoma/lymphoma, prion‐mediated transmissible spongiform encephalopathies (e.g.
Creutzfeldt–Jakob) and Castleman disease. A further understanding of FDCs and their functions in both health and disease may
aid our ability to better regulate immunity and ameliorate some disease states.

Key Concepts

FDCs trap antigens as immune complexes that consist of antigen in the presence of either specific antibodies or complement
proteins, or both. FDCs trap immune complexes using CD32 and/or CD21.

FDC‐trapped antigens or iccosomes are highly immunogenic and minute amounts (picogram) can induce significant quantities (microgram)
of a specific antibody.

FDC‐trapped antigens remain on the surface of FDCs and are not internalised. These antigens are not degraded but maintain
their native configuration and immunoreactivity for many months.

Figure 2. FDCs trapping fluorescently labelled ICs in vivo and in vitro. (a) Photomicrograph of FDCs in vivo demonstrating trapping of ovalbumin ICs (ovalbumin + antiovalbumin). The ICs on FDCs are detected using goat antibody directed
against the antiovalbumin present in the immune complexes (i.e. goat‐anti‐IgG (blue)). The arrows designate two FDC networks
containing trapped fluorescent ICs. (b) FDC‐trapping of fluorescent antigen in vitro. Ovalbumin ICs were incubated with highly enriched FDCs in culture. Detection of the FDC‐trapped antigen is performed using
goat antibody specific for the IgG in the ovalbumin–anti‐ovalbumin complexes (red) and the FDCs are labelled using FDC‐M1
(blue). (c) Higher magnification of an isolated FDC with ICs labelled as in panel b. Contributed by Dr. John G. Tew.

Figure 3. Important FDC‐membrane‐associated signalling molecules. In experimental animals with specific Abs, ICs form instantaneously
upon Ag challenge and are trapped by FDC‐Fcγ RIIB and CR1/2. The engagement of FDC‐FcγRIIB with ICs provides signals to FDCs
that result in the production of BAFF and IL‐6. These same ICs also activate complement and generate C3 and C4 fragments that
are covalently bound to FDC‐ICs and can also be seen ‘decorating’ the FDC membranes. C3 fragments (CD21 ligand) engage FDC‐CR1/2,
whereas C4BP binds C4b and localises on the FDC‐ICs. The periodically arranged FDC‐ICs engage BCRs, and extensive BCR cross‐linking
delivers an Ag‐specific stimulatory signal. FDC‐CD21‐ligand binds B‐cell CD21, FDC‐C4BP ligates B‐cell CD40, FDC‐BAFF engages
B‐cell BAFF‐R, and FDC IL‐6 binds B‐cell IL‐6R, delivering additional co‐stimulatory signals that promote B‐cell activation,
proliferation and differentiation. Contributed by Dr. John G. Tew.

Figure 4. FDC contributions in health and disease. FDCs serve as a repository of retained antigens important in maintaining IgG and
IgE memory responses. In addition, FDCs provide signs that promote the germinal centre (GC) reaction and license macrophages
(MO) to destroy and remove apoptotic cells from the GC. In disease, FDCs also play important roles, serving as a reservoir
of infectious HIV, and a source of PrPC, the normal form of the prion protein. Furthermore, these cells appear to play roles in some malignancies and in Castleman
disease.

Humphrey JH, Grennan D and Sundaram V (1984) The origin of follicular dendritic cells in the mouse and the mechanism of trapping of immune complexes on them. European Journal of Immunology 14: 859–864.